Total Artificial Heart Implantation Blood Pressure Management as Resolving Treatment for Massive Hemolysis following Total Artificial Heart Implantation.

The SynCardia Total Artificial Heart (TAH) has been used for patients with biventricular failure, who cannot be managed with implantation of a left ventricular (LV) assist device. Following TAH implantation, our patient developed severe hemolysis, which could only be managed successfully by aggressive blood pressure control [Ohashi 2003; Nakata 1998].

Alternatives to heart transplantation. Symposium of the "Treatment of End-stage Heart and Lung Failure" working group on October 22, 2005 in Munich.

Heart transplantation is currently the treatment of first choice in patients with end-stage refractory heart failure. But already the demand for donor organs cannot be met, and patients face long waiting times for transplantation. In the future waiting times will become even longer as life expectancy increases and the number of heart-failure patients requiring transplantation grows. Consequently, in view of the poor prognosis of the disease in its advanced stages, alternatives to heart transplantation are increasingly gaining importance. In recent years new innovative treatment methods and techniques have been developed which have already proved clinically successful in patients with end-stage heart failure, especially as bridging measures. Some of these techniques appear suitable for long-term use and could therefore serve as an alternative to heart transplantation in some patients. Interesting new avenues of research may even lead to cardiac cell replacement therapies in the future. These approaches are currently undergoing initial clinical trials. This report presents surgical and cardiologic treatments for end-stage heart failure that have already been clinically investigated as well as techniques that are still in the preclinical stage and discusses their potential as alternatives to heart transplantation.

Implantation of CardioWest total artificial heart for irreversible acute myocardial infarction shock.

Patients who develop cardiogenic shock after acute myocardial infarction have a very high mortality rate despite early reperfusion therapy. Hemodynamic stabilization can often only be achieved by implanting a mechanical circulatory support system. When, in cases representing expansive myocardial impairment without any chance of recovery, pharmacological therapy and the use of percutaneous assist devices have failed, the implantation of a total artificial heart is indicated. We report our first experiences with this extensive and innovative method of managing irreversible cardiogenic shock patients. The CardioWest total artificial heart was implanted in 5 patients (male; mean age, 50 years). All patients were in irreversible cardiogenic shock despite maximum dosages of catecholamines, an intra-aortic balloon pump and/or a femoro-femoral bypass. In all patients early reperfusion therapy was performed. After implantation of the Cardio West system, all dysfunctional organ systems rapidly recovered in all patients. Four of 5 patients underwent successful heart transplantation after a mean support time of 156 days. One patient died because of enterocolic necroses caused by an embolic event after termination of dicumarol therapy. In summary, our first experiences justify this extensive management in young patients who would otherwise have died within a few hours.

IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.

Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.

First use of the Molecular Adsorbent Recirculating System technique on patients with hypoxic liver failure after cardiogenic shock.

The Molecular Adsorbent Recirculating System (MARS) has been proven to prolong survival in patients with hepatorenal syndrome. MARS is a modified dialysis that uses an albumin containing dialysate, which is recirculated and perfused online through charcoal and anion exchanger columns. It allows the selective removal of albumin bound substances. Despite advances in medical therapy and technology, the prognosis of patients with cardiogenic shock remains poor. Mortality rates are as high as 80%, often because of persistent multiple organ failure. To determine whether patients with hypoxic liver failure after cardiogenic shock after cardiac surgery might benefit from MARS, we performed a prospective, randomized, controlled, single center study. The primary objective was to prove that MARS improves survival. This article is a report on the interim analysis of the first 27 patients included between August 2000 and December 2001; 14 patients were in the MARS group, and 13 patients were in the non-MARS group. All had bilirubin levels greater than 8 mg/ml. Both groups had a similar risk profile. The MARS group received MARS for 3 consecutive days-if bilirubin was still greater than 6 mg/dl afterward, MARS was continued. The non-MARS group received conventional therapy. We had seven survivors in the MARS group (50%) compared with four (32%; p = ns) in the non-MARS group. We conclude that despite the limited number of patients included in this analysis, MARS can be recommended for patients with acute, hypoxic liver failure because it might prolong survival. Further studies in similar patient cohorts are needed to verify our results.

[Mechanical circulatory support: 15 years of experience in the Heart Center North Rhine-Westphalia]. / Mechanische Kreislaufunterstützung--15 Jahre Erfahrung im Herzzentrum Nordrhein-Westfalen.

OBJECTIVES: Against the background of an increasing number of patients suffering from severe congestive heart failure, mechanical circulatory support becomes more and more important. The indications for this therapeutic option ranges from bridging to cardiac transplantation, the application of the most recent systems as an alternative to transplantation, as well as in cardiogenic shock following open-heart surgery, acute myocardial infarction of fulminant myocarditis. PATIENTS AND METHODS: Between September 1987 and November 2002, 670 implantations of 11 different mechanical circulatory support systems were performed in 607 patients (125 women, 482 men, age 1 month - 82 years). 255 patients received the device as a bridge to recovery (BTR) of their native organ, 276 patients as a bridge to cardiac transplantation (BTT), 49 patients as an emergency measure in life-threatening cardiogenic shock (bridge-to-bridge, BTB), and 27 patients as an alternative to transplantation (ATT). RESULTS: 38% of the BTR group, 56% of the BTT group, 34% of the BTB group and 27% of the ATT group underwent successful cardiac transplantation or could be discharged from hospital. Infections and thromboembolic events were the most frequent complications but decreased with increasing experience and sophistication of devices. Some systems offer the possibility of discharging patients home while on the device. In our cohort, 90 patients left the hospital on support for a mean duration of 204 days. Readmission rate after 200 days was 50% and was system-related in less than 6%. CONCLUSIONS: In spite of a still considerable morbidity associated with the employment of mechanical circulatory support, the results are encouraging and justify the high economic burden.

Outcome of heart transplantation in patients previously infected with hepatitis C virus.

The lack of knowledge about the course of hepatitis C virus infection (HCV) before heart transplantation (HTx) prompted us to describe our experience with 4 such patients who presented with positive HCV serology before surgery. Two experienced non-liver related deaths at 3.5 and 5 years after HTx, and none of the patients developed signs of hepatic insufficiency during the follow-up (mean 3.8 years). Tests for HCV antibodies were frequently negative, whereas viral RNA was detected in 81% of the measurements, showing that virus detection techniques seem to be more sensitive than serology techniques in detecting HCV infection in this group of patients. Although immunosuppression promotes active HCV replication, it does not seem to change the chronic features of HCV infection during the first years in patients with good liver function.

Device and patient management in a bridge-to-transplant setting.

BACKGROUND: A variety of sophisticated devices have been developed for mechanical circulatory support in patients bridged to cardiac transplantation. Based on 13 years' experience, we have developed specific protocols for patient selection and management for different devices. METHODS: The principal systems applied in the bridge-to-transplant cohort are the Thoratec ventricular assist device (n = 144, mean duration of support 53 +/- 57 days), the Novacor left ventricular assist system (LVAS) (n = 85, mean duration of support 154 +/- 15 days), and the HeartMate LVAS (n = 54, mean duration of support 143 +/- 142 days). The Thoratec device is used for biventricular assistance or if the duration of support is expected to be less than 6 months. For long-term support, either the Novacor or HeartMate LVAS are preferred. RESULTS: Despite careful postoperative patient management, this group of patients is prone to a variety of complications. Bleeding occurred in 22% to 35%, right heart failure in 15% to 26%, neurologic disorders in 7% to 28%, infection in 7% to 30%, and liver failure in 11% to 20% of patients. Complications varied with the device applied and the patient's preoperative condition. A total of 73 patients were discharged from hospital for a mean period of 184 days; this cumulative experience amounted to 37.5 patient-years. CONCLUSIONS: The Novacor and the HeartMate systems offer the additional possibility of discharging patients during support if they fulfill certain criteria. The main reasons for rehospitalization were thromboembolic and infectious complications.

[INR self-management after mechanical heart valve replacement: ESCAT (Early Self-Controlled Anticoagulation Trial)]. / INR-Selbstmanagement nach mechanischem Herzklappenersatz: ESCAT (Early Self-Controlled Anticoagulation Trial).

Severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement essentially occur due to intense oral anticoagulation and fluctuating individual INR values around the target range. INR self-management can help to minimize these fluctuations. Beginning this therapeutic control immediately after mechanical heart valve replacement further reduces anticoagulant-induced complications. Included in the study were 1200 patients. The quality of oral anticoagulation also improved through INR self-management. Over an observation period of two years, nearly 80% of INR values recorded by the patients themselves were within the target therapeutic range of 2.5-4.5. This corresponds to a high significance of p < = 0.001 in favor of INR self-management. Only 64.9% of INR values monitored by family practitioners were within the desired range. The results differed slightly in quality between patient groups with different levels of training (comprehensive, secondary modern, grammar with or without university). Of patients trained in INR self-management following mechanical heart valve replacement, 91.7% maintained their competence in this technique throughout the entire follow-up period. Only 8.3% of those trained immediately after surgery were unable to continue with INR self-management.

[INR Self-management after mechanical heart valve replacement: ESCAT (Early Self-Controlled Anticoagulation Trial)]. / INR-Selbstmanagement nach mechanischem Herzklappenersatz: ESCAT (Early Self-Controlled Anticoagulation Trial).

Severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement essentially occur due to intense oral anticoagulation and fluctuating individual INR values around the target range. INR self-management can help to minimize these fluctuations. Beginning this therapeutic control immediately after mechanical heart valve replacement further reduces anticoagulant-induced complications. Included in the study were 1200 patients. The quality of oral anticoagulation also improved through INR self-management. Over an observation period of two years, nearly 80 % of INR values recorded by the patients themselves were within the target therapeutic range of 2.5-4.5. This corresponds to a high significance of p < = 0.001 in favor of INR self-management. Only 64.9 % of INR values monitored by family practitioners were within the desired range. The results differed slightly in quality between patient groups with different levels of training (comprehensive, secondary modern, grammar with or without university). Of patients trained in INR self-management following mechanical heart valve replacement, 91.7 % maintained their competence in this technique throughout the entire follow-up period. Only 8.3 % of those trained immediately after surgery were unable to continue with INR self-management.

Novacor left ventricular assist system versus Heartmate vented electric left ventricular assist system as a long-term mechanical circulatory support device in bridging patients: a prospective study.

OBJECTIVE: Long-term mechanical circulatory support as a bridge-to-transplantation procedure and bridge to recovery is of increasing importance. The implantable left ventricular assist devices, Novacor N100 left ventricular assist system (Baxter Healthcare Corporation, Berkeley, Calif) and TCI HeartMate vented electric left ventricular assist system (Thermo Cardiosystems Inc, Woburn, Mass), have proved to be efficient devices in bridge-to-transplantation settings and for prolonged support. The two systems were compared with regard to reliability and morbidity. METHODS: Between October 1996 and March 1998, a prospective, single-center study was done that included 40 patients, 20 of whom were treated with the Novacor system and 20 of whom were treated with the HeartMate device. The diseases were mainly dilated cardiomyopathy (13/9) and ischemic cardiomyopathy (6/10). There were no statistically significant differences between the two groups regarding age, sex, preoperative clinical blood chemistry values, hemodynamic data, or risk factors. RESULTS: There were no statistically significant differences between the two groups with regard to postoperative hemodynamics, organ recovery, out-of-hospital support, and survival to heart transplantation. Mean duration of support was 235.3 +/- 210 days for the Novacor group and 174.6 +/- 175 days for the HeartMate group and mean out-of-hospital support was 241 +/- 179 days and 166 +/- 152 days for the two groups, respectively. Neurologic complications occurred significantly more often among the Novacor group, whereas the HeartMate group had a higher prevalence of infections and technical problems, which was statistically significant. Survival to transplantation was 65% for the Novacor group and 60% for the HeartMate group. CONCLUSIONS: Most patients had organ recovery with left ventricular assist system support, and a considerable number of patients in both groups underwent transplantation. However, both devices need revision to address the current problems, that is, thromboembolism for the Novacor device and infection and reliability for the HeartMate device.

Single-center experience with the thoratec ventricular assist device.

OBJECTIVE: The Thoratec ventricular assist device (Thoratec Laboratories, Pleasanton, Calif) is widely accepted for univentricular and biventricular support in patients with various indications. The aim of this study is to describe our experience with implantation of the Thoratec ventricular assist device in more than 100 patients. METHODS: From March 1992 to June 1998, 114 patients (98 men and 16 women; mean age, 47.9 years) received the Thoratec ventricular assist device for a mean duration of 44.9 days. The patients were divided into 3 groups. Group 1 included 84 patients in whom the system was applied as a bridge-to-transplant procedure. Group 2 included 17 patients with postcardiotomy cardiogenic shock, and group 3 included 13 patients with cardiogenic shock of other causes. RESULTS: Sixty-eight percent of patients in group 1 survived to transplantation with a posttransplant survival of 88%. The only independent risk factor affecting survival was age more than 60 years. Survivals in groups 2 and 3 were 47% and 31%, respectively. Main complications in all groups were bleeding, multiple organ failure, liver failure, sepsis, and neurologic disorders. CONCLUSIONS: The Thoratec ventricular assist device has proved to be a reliable device for bridge to transplantation and postcardiotomy support. Further studies are required on patient selection and on patient and device management to reduce the incidence of complications in these patient populations.

Implantation of the Biomedicus centrifugal pump in post-transplant right heart failure.

BACKGROUND: Right heart failure after heart transplantation represents a life-threatening complication. When conventional therapy including NO-inhalation fails the only choice to reach sufficient haemodynamic conditions may be the implantation of a right ventricular support system. METHODS: In all cases the Biomedicus centrifugal pump was implanted by cannulation of the right atrium and pulmonary artery. RESULTS: Since March 1989 950 heart transplant procedures were performed at our center. In nine cases (7 male, 2 female, mean age 52 years) implantation of a right ventricular support system was necessary because of deterioration of right ventricular function. The implantation was carried out in 7 cases immediately after transplantation, in 2 cases after 2 days. The support time ranged from 4-348 hours. Six patients could be weaned, 2 patients underwent retransplantation and died and 1 patient died on the support system. Three of the six weaned patients died in the further course because of multiorgan failure. CONCLUSIONS: Mechanical right ventricular support is often the only therapeutical tool to reach adequate haemodynamic conditions in post-transplant right heart failure. The Biomedicus centrifugal pump provides good conditions in these cases. Weaning is often possible after short-term support. The mortality rate is determined by multiorgan failure in immuno-suppressed patients. Retransplantation seems not to be successful despite maximal treatment.

A novel method to reduce device-related infections in patients supported with the HeartMate device.

Improved implantable left ventricular assist device technology has made survival to heart transplantation a near certainty. Nevertheless, infection remains a major risk to recipients of current percutaneous systems. We developed a modified implantation technique applied to the last 9 of 30 patients who received the HeartMate vented electric left ventricular assist system (LVAS). Covering the upper surface of the pump with a patch of knitted graft material was followed by a decline in the incidence of pocket infections from 33.3% to 11.1%. This modification compares favorably to that of a lengthened percutaneous driveline tunnel in reducing device-related infection.

New technique for the outflow cannulation of right ventricular assist device.

Cannulating the outflow cannula of a right ventricular assist device (RVAD) through the main pulmonary artery is often troublesome because of extensive dissecting adhesion. We implanted RVADs using the new technique for outflow cannulating through the right pulmonary artery between the ascending aorta and the superior vena cava. With this technique, we needed only a little dissection and no cardiopulmonary bypass. This technique could make RVAD implantation simple, quick, and safe.

Temporary pulsatile ventricular assist devices and biventricular assist devices.

BACKGROUND: During the past years several systems for mechanical circulatory support have become available. In this study we describe our experience with short-term and mid-term application of the ABIOMED and Thoratec device. METHODS: Since 1990 the ABIOMED BVS and since 1992 the Thoratec VAD have been applied to 75 and 103 patients, respectively, with postcardiotomy heart failure, as a bridge-to-transplant procedure, and with different other indications. RESULTS: In the ABIOMED collective 25 of 50 patients (50%) with postcardiotomy heart failure and 1 of 4 patients with miscellaneous other indications could be discharged from hospital, 7 of 14 bridge-to-transplant patients (50%) underwent transplantation with a posttransplant survival of 86%. In the Thoratec collective 6 of 10 patients (60%) with postcardiotomy heart failure and 4 of 8 patients (50%) with miscellaneous indications could be discharged from hospital, 48 bridge-to-transplant patients (74%) underwent transplantation with a posttransplant survival of 90%. CONCLUSIONS: The results show the versatility of the Thoratec VAD for short-term and mid-term application in patients with postcardiotomy heart failure and as a bridge-to-transplant procedure. The use of the ABIOMED device is not indicated for bridging patients to transplantation. Although in case of postcardiotomy heart failure, Thoratec is also superior to ABIOMED, the high costs of the Thoratec VAD limits its wide acceptance in this patient cohort.

The European experience of Novacor left ventricular assist (LVAS) therapy as a bridge to transplant: a retrospective multi-centre study.

OBJECTIVE: Artificial heart devices have suffered from a negative press based on the early Jarvik experience of the 1980s. This is in stark contrast to realities of current left ventricular assist (LVAS) therapy. The Novacor N100 PC wearable left ventricular assist system (LVAS) was introduced in Europe in late 1993. This system allows implanted recipients to be completely autonomous with the system controlled by a small computer and powered by rechargeable batteries. This report represents the initial European experience with the Novacor LVAS. METHODS: Since the system was introduced with regulatory approval as a commercial product, clinicians were not bound by the constraints of a study protocol and only minimal data were collected. This report presents the results of a retrospective study of 118 consecutive patients who had the LVAS implanted as a bridge to transplant, in 19 centres over the three year period ending in November 1996. RESULTS: Mortality and morbidity varied widely between centres. The median implant time was 115 days (0-585 days) and 33% of patients returned home, supported by the LVAS. The overall survival on LVAS was 64%. The major causes of death were infection (14%) and MOF (6%). There were no significant device or system failures despite a cumulative patient experience of 24.8 years outside of a hospital environment. Patient selection and management varied greatly between centres and this was reflected in disparate outcomes. CONCLUSIONS: Optimal selection and management of LVAS patients has still to be established. While the data available for this report lacked the detail necessary to demonstrate direct causal relationships between selection and management, it was clear from the inter-centre differences that these two factors have a major impact on outcomes. This early experience has directed attention towards improved management regimes. Given the results obtained from the best centres and the ability to discharge patients to lead near-normal lives in the community, the authors believe that the Novacor LVAS now offers a real therapeutic alternative for selected end-stage heart failure patients for whom a donor heart is unavailable or who are unsuitable for transplantation.

Altered levels of mRNA of apoptosis-mediating genes after mid-term mechanical ventricular support in dilative cardiomyopathy--first results of the Halle Assist Induced Recovery Study (HAIR).

BACKGROUND: Ventricular assist devices (VADs) lead to an immediate unloading of the failing heart. Although VADs are used as a bridge to transplant, in some cases patients suffering from dilated cardiomyopathy have been weaned from the VAD without transplantation after a recovery process initiated by the cardiac support. Myocardial apoptosis is associated with inadequate myocardium and might be reverted during VAD support of the failing heart. Therefore we measured transcription of apoptosis-associated genes FasExo6 Del, Fas-receptor, and Bcl-xL as markers of a putative recovery. METHODS: Fas-receptor, its soluble isoform FasExo6Del, and Bcl-xL mRNA were quantified by standard calibrated competitive reverse-transcription polymerase chain reaction (PCR) in 6 patients suffering from dilated cardiomyopathy. RNA standards were prepared by introducing 100 bp deletions into the native cDNA, resulting in truncated PCR products with identical primer-binding sites. Standards were transcribed in vitro and the resulting RNA was quantified. RESULTS: Transcription of apoptosis-inhibiting genes FasExo6 Del and Bcl-xL were upregulated in patients supported for more than 6 weeks. Fas receptor mRNA remained unaffected by VAD support. CONCLUSIONS: Transcriptional upregulation of apoptosis-inhibiting genes might be caused by a desensitization to apoptotic stimuli and might indicate a relaxation of the diseased status of the myocardium. These data outline the first biochemical evidence of a remodelling process occurring in supported ventricular myocardium.

Mechanical circulatory support after orthotopic heart transplantation.

Frequently the only therapy for primary graft- and right heart failure, as well as low output syndrome from acute of chronic rejection, is implantation of a mechanical circulatory support system, until recompensation or retransplantation. At our institution, mechanical assist devices were implanted in 25 heart recipients for a cute rejection (n=9), primary graft failure (n=7), acute right heart failure (n=7), and chronic rejection with low output syndrome (n=2). Patients (pts) with primary graft failure (n=3) received an intraaortic balloon pump (IABP), one pt an IABP plus Abiomed-System for left ventricular support, one pt the Thoratec-System for biventricular support. Patients with right heart failure (RHF) received the Biomedicus centrifugal pump for right ventricular support. Nine pts suffered from acute rejection. Six pts received an IABP, one the Biomedicus as femoro-femoral bypass, one the Abiomed-System for biventricular support, two the Thoratec-System for biventricular support and two within this group switched from the Biomedicus pump to the Thoratec-System for biventricular support. Patients with chronic graft failure (n=2) received the Novacor-System (LVAD) for left ventricular support, one received a Tojobo-System and an oxygenator for biventricular support post coronary artery bypass surgery. Support time ranged from 0.5-h to 73 days. Five pts were weaned. Two (8%) of 25 pts were retransplanted, 18 (72%) died in spite of mechanical support from multiple organ failure. The use of a mechanical assist device after heart transplantation is encouraging only in the case of early right heart failure, as well as primary and chronic graft failure. In view of the poor results, the use of mechanical assist devices should not be recommended in the case of heart failure caused by acute rejection.